Though neither sex held an advantage in terms of death, myocardial infarction, revascularization, or stent thrombosis at 2 years, women "showed a significantly higher prevalence of clinically relevant chest pain, which might be largely related to mechanisms other than epicardial coronary obstruction," the researchers concluded.

"Microvascular dysfunction, which is known to be more prevalent in women, might account for this gender difference," suggested von Birgelen's group. "Female patients with unstable coronary syndromes show more electrocardiographic changes despite having a lower prevalence of epicardial obstructions than men, which suggests a higher prevalence of microvascular dysfunction in women."

Yet Jennifer A. Tremmel, MD, MS, of California's Stanford University Medical Center, was not so accepting of the microvascular dysfunction explanation.

She cited the WISE study, since which "we have gone from assuming that angina in the absence of obstructive coronary artery disease is non-cardiac to assuming it is microvascular dysfunction," she wrote in an accompanying editorial. "There are several other possibilities, and without actually testing for the cause of chest pain following percutaneous coronary intervention [PCI], we are left not knowing."

And "while the overall prevalence of microvascular dysfunction is presumed to be higher in women than men ... this has never been proven, and among similarly presenting women and men, there does not appear to be a sex difference in microvascular dysfunction," Tremmel noted.

"At some point, we have to stop reporting that women have more chest pain than men, and start answering why and what to do about it," she emphasized.

The present investigation included 3,202 Dutch patients enrolled in TWENTE and DUTCH PEERS. The two trials together included patients receiving either zotarolimus- or everolimus-eluting stents between 2008 and 2012.

"Over 10% of patients who presumably have their problem 'fixed' with PCI continue to have chest pain with activities of daily living," according to the editorialist. "Clearly, we need a better understanding of the non-obstructive causes of chest pain in patients following stent placement."

The authors suggested that, for now, bioresorbable vascular scaffolds (BVS) may alleviate the recurrence of chest pain after PCI, because these "show a superior compliance to the dynamics of the vessel wall and cause less vessel stretch than contemporary metallic DES" as well as allowing vasomotion.

Von Birgelen and colleagues acknowledged that their data was "not powered to detect outcome differences between women and men" nor were the data sufficient with regards to anti-anginal medication, completeness of revascularization, angiography, or stress testing, however.

Additionally, they did not use a standard survey for chest pain, instead opting for a self-designed questionnaire.

This endpoint is particularly vexing to begin with, as chest pain is "problematic" to define, a "subjective experience not easily transformed into an objective variable," Tremmel wrote. "Our traditional classification systems are completely lacking, and this undoubtedly affects our ability to perform optimal clinical care and research."

For now, "in women, the presence of chest pain after successful PCI with newer generation DES often does not indicate a failure of interventional treatment," the authors concluded.

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